A major component of morbidity and mortality attributable to cardiovascular disease occurs as a consequence of the partial or complete blockage of vessels carrying blood in the coronary or peripheral vasculature. When such vessels are partially occluded, lack of blood flow causes ischemia to the muscle tissues supplied by such vessel, consequently inhibiting muscle contraction and proper function. Total occlusion of blood flow causes necrosis of the muscle tissue.
Blood vessel occlusions are commonly treated by mechanically enhancing blood flow in the affected vessels. Such mechanical enhancements often employ surgical techniques that attach natural or synthetic conduits around the occlusion, thereby providing bypass grafts, or employ revascularization by various means to physically enlarge the vascular lumen at the site of occlusion. Significant morbidity and even mortality frequently accompany surgical approaches.
Balloon angioplasty is utilized as an alternative to bypass surgery for treatment early in the development of stenosis or occlusion of blood vessels due to the abnormal build-up of plaque on the endothelial wall of a blood vessel. Angioplasty typically involves guiding a catheter that is usually fitted with a balloon through an artery to the region of stenosis or occlusion, followed by brief inflation of the balloon to push the obstructing intravascular material or plaque against the endothelial wall of the vessel, thereby compressing or breaking apart the plaque and reestablishing blood flow. In some cases, particularly where a blood vessel may be perceived to be weakened, a stent is deployed.
Balloon angioplasty and stent deployment, however, may result in injury to a wall of a blood vessel and its endothelial lining. For example, undesirable results such as denudation (removal) of the endothelial cell layer in the region of the angioplasty, dissection of part of the inner vessel wall from the remainder of the vessel wall with the accompanying occlusion of the vessel, or rupture of the tunica intima layer of the vessel may occur. A functioning endothelial reduces or mitigates thrombogenicity, inflammatory response, and neointimal proliferation.
Attempts to treat or reduce injury to the vessel wall resulting from stent or balloon deployment as well as the ischemia or restenosis to tissue regions resulting from the occlusion have included systemic and local delivery of therapeutics. Systemic delivery, however, has several disadvantages. In particular, in systemic delivery techniques, the whole organism is treated therefore greater amounts of drugs must be supplied which are sometimes toxic to the organism.
Local delivery techniques may be used to overcome some of the disadvantages of systemic delivery techniques, however, a separate set of problems arise. Typically, in local delivery techniques, a treatment agent is injected into a blood stream or healthy vessel region at a point upstream from the treatment site or into an unperfused vessel region after first occluding the vessel region to inhibit blood flow. In either case, otherwise healthy vessel regions are traumatized in order to treat the injured tissue region.